Objective To investigate the short-term therapeutic effect of liraglutide injection combined with insulin pump subcutaneous infusion of insulin in the treatment of early-onset obesity.Methods 100 patients with diabetes mellitus treated with endocrine specialist outpatients from May 2015 to August 2016 in our hospital were selected and randomly divided into three groups,insulin+liraglutide injection 1.2 mg/d group(treatment group 1),insulin+metformin 0.5 tid group(treatment group 2)and insulin intensive group(control group).The control group of 20 cases,the remaining 40 cases each group.Each patient was treated with their own treatment regimen.Target blood glucose: fasting blood glucose≤7.0mmol/L,2h postprandial blood glucose≤10mmol/L that is compliance,blood glucose≤4.4mmol/L that low,blood glucose≤3.9mmol/L that low blood sugar.Two groups of patients adhere to three months of treatment.At the time of admission,after 2 weeks of treatment and 6 months of treatment,venous blood was taken for biochemical examination.The corresponding biochemical indicators were compared and the therapeutic effects of the two regimens were compared.Results There were significant differences in the levels of fasting glucagon,fasting C-peptide and body mass index between the two groups after three weeks of treatment and three months after treatment(P<0.05).The total amount of insulin,the time of reaching the standard and the frequency of hypoglycemia of three groups were compared,the difference was statistically significant(P<0.05).Conclusion Using three kinds of treatment for the treatment of elderly obese diabetesmellitus have a significant effect.However,the treatment regimen of insulin+liraglutideinjection 1.2 mg/d is effective in the control of diabetes and the total insulin dosage,as well as the number of hypoglycemia occurred,are better than the other two groups of treatment.

Filamentous fungi are important industrial microorganisms that play important roles in the production of bio-based products such as organic acids, proteins and secondary metabolites. The development of metabolic engineering and its enabling techniques have greatly promoted the design, construction and application of filamentous fungal cell factories. This article systematically reviews the development of filamentous fungal cell factories constructed through metabolic engineering, and discusses the challenges and future perspectives for systems metabolic engineering of filamentous fungi.
Fungi/genetics* ; Metabolic Engineering

OBJECTIVE To study the pharmacokinetic changes in the plasma and cerebrospinal fluid of bronchial asthma model rats after the complication of Ephedra sinica and Prunus armeniaca. METHODS SD male rats were randomly divided into blank group， model group， E. sinica group （12 g/kg， calculated by raw drug， similarly hereinafter）， P. armeniaca group （6 g/kg） and E. sinica-P. armeniaca drug-pair group （12 g/kg of E. sinica+6 g/kg of P. armeniaca）， with 6 rats in each group. Except for the blank group， the bronchial asthma model was induced by spraying rats in each group with an equal volume mixture of 2% acetylcholine chloride and 0.4% histamine phosphate， once a day， for 7 d. One hour before modeling every time， rats in each group were gavaged with the corresponding drug/normal saline， once a day， for 7 d. After the final administration and provocation of asthma， blood and cerebrospinal fluid collection were performed at different time points. The plasma and cerebrospinal fluid samples were pre-treated （with geranylgeranyl as the internal standard）， and the mass concentrations of ephedrine/pseudoephedrine， methyl ephedrine and amygdalin in both samples were determined by liquid chromatography-tandem mass spectrometry. DAS 2.0 pharmacokinetic software was used to determine the main pharmacokinetic parameters through the non-atrial chamber model and to compare the changes of the pharmacokinetic parameters before and after the combination of the two drugs. RESULTS Compared with E. sinica group， cmax and AUC0-21.33 h （or AUC0-10.67 h） of ephedrine/pseudoephedrine and methyl ephedrine in the plasma and cerebrospinal fluid of rats were significantly reduced in E. sinica-P. armeniaca drug-pair group， while CLZ/F and VZ/F were significantly increased （P＜0.05 or P＜0.01）； tmax of methyl ephedrine in the cerebrospinal fluid was significantly shortened （P＜ 0.05）.Compared with P. armeniaca group， the t1/2 of amygdalin in the plasma of rats in E. sinica-P. armeniaca drug-pair group was significantly shortened， and CLZ/F was significantly increased （P＜0.01）； the tmax of bitter amygdalin in the cerebrospinal fluid was significantly shortened， and the AUC0-10.67 h， CLZ/F， and VZ/F were significantly increased （P＜0.01）. CONCLUSIONS The combination of E. sinica and P. armeniaca accelerates the absorption and elimination of ephedra alkaloids， thus reducing the accumulation of ephedra alkaloids in the bronchial asthma model rats.